Biological Evaluation of Noscapine analogues as Potent and Microtubule-Targeted Anticancer Agents

Abstract

In present investigation, an attempt was undertaken to modify the C-9 position of noscapine (Nos), an opium alkaloid to yield 9 -hydroxy methyl and 9 -carbaldehyde oxime analogues for augmenting anticancer potential. The synthesis of 9-hydroxy methyl analogue of Nos was carried out by Blanc reaction and 9-carbaldehyde oxime was engineered by oxime formation method and characterized using FT-IR, 1H NMR, 13C NMR, mass spectroscopy, and so on techniques. In silico docking techniques informed that 9-hydroxy methyl and 9-carbaldehyde oxime analogues of Nos had higher binding energy score as compared to Nos. The IC50 of Nos was estimated to be 46.8 µM signficantly (P < 0.05) higher than 8.2 µM of 9-carbaldehyde oxime and 4.6 µM of 9-hydroxy methyl analogue of Nos in U87, human glioblastoma cells. Moreover, there was significant (P < 0.05) difference between the IC50 of 9-carbaldehyde oxime and 9-hydroxy methyl analogue of Nos. Consistent to in vitro cytotoxicity data, 9-hydroxy methyl analogue of Nos induced significantly (P < 0.05) higher degree of apoptosis of 84.6% in U87 cells as compared to 78.5% and 64.3% demonstrated by 9-carbaldehyde oxime and Nos, respectively. Thus the higher therapeutic efficacy of 9-hydroxy methyl analogue of Nos may be credited to higher solubility and inhibitory constant (K).

Molecular encapsulation of andrographolide in 2-hydroxypropyl-β-cyclodextrin cavity: synthesis, characterization, pharmacokinetic and in vitro antiviral activity analysis against SARS-CoV-2

“…The AND-2-HyP- β -CYD complex did not show any cytotoxcity to Vero E6 cells at 10 μ g.mL -1 or 100 μ g.mL -1 , measured by MTT assay [ 24 ]. AND-2-HyP- β -CYD complex at the concentration of 9 mg.mL -1 demonstrated 85.97 % (E) and 85.89 % (N) inhibition of Vero E6 cells infected with SARS-CoV-2 at 24 h remarkably (One-Way-ANOVA test, P<0.05) higher than 72.26 % (E) and 77.61 % (N) presented by standard drug, remdesivir ( Table 3 ).…”

“…The cytotoxic effect of AND-2-HyP- β -CYD complex on the property of Vero E6 cells was evaluated by using MTT dye [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay technique [ 24 ]. In brief, 1x10 4 Vero E6 cells were incubated for 24 h in serum DMEM (Dulbecco’s Modified Eagle Medium) of about 200- μ l in a 96 wells microtiter plate.…”

Bioengineering of Anti‐Inflammatory Natural Products

“…The biosynthesis of noscapine ( 5 ) starts from l ‐tyrosine ( 6 ) and proceeds via the intermediate reticuline ( 7 ). Residues that were successfully modified in reticuline and noscapine by biotechnological or semisynthetic methods are highlighted [90–102,105,106,108] …”

“…In the past 10 years, several attempts have been made to generate noscapine analogues with favorable properties. [91][92][93][94][95][96][97][98][99][100][101][102] As a consequence of the complex stereochemistry, total chemical syntheses of noscapinoids are hard to realize. Therefore, semisynthesis has become the method of choice.…”

“…Residues that were successfully modified in reticuline and noscapine by biotechnological or semisynthetic methods are highlighted. [90][91][92][93][94][95][96][97][98][99][100][101][102]105,106,108] The biotechnological production of noscapine analogues became possible following the discovery and characterization of its biosynthesis gene cluster in the opium poppy. [103,104] The natural assembly of 5 is extremely complex.…”